Using biophysical methods and chemical biology to explore function and design in the tandem-repeat protein class

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Theme: World-Class Underpinning BioscienceThe major focus of our research is a class of proteins, known as tandem-repeat proteins, with very distinctive architecture (e.g. ankyrin, tetratricopeptide and armadillo repeats). These proteins are frequently deregulated in human diseases such as cancers and respiratory and cardiovascular diseases. The individual modules of repeat proteins stack in a linear fashion to produce highly elongated, superhelical structures, thereby presenting an extended scaffold for molecular recognition. The term 'scaffold' implies a rigid architecture; however, as suggested by their Slinky spring-like shapes, it is thought that repeat arrays utilise much more dynamic and elastic modes of action. The simple modular architecture of repeat proteins makes them uniquely amenable to the dissection of their biophysical properties as well as the rational redesign of these properties. The PhD project will continue from the rotation project with the goals of grafting new functions into repeat-protein scaffolds. Key techniques will be protein engineering, biophysical analysis and X-ray crystallography. Cell biology will be used to test the designed proteins and their function. We are also thinking about a collaborative project with Dr. Luca Pellegrini (Department of Biochemistry).ENWW will mainly involve statistical analysis of experimental data. For this purpose, statistical tools, such as R, will be used.